The Role of Lateral Septal Opioid and GABAA Receptors in Feeding Behavior

Morphine, a µ opioid agonist, elicits eating in rats when injected into multiple brain regions related to feeding and reward including the ventral tegmental area (VTA), nucleus accumbens shell and multiple regions of the hypothalamus (Castro & Berridge, 2014). It produces a particularly large feeding effect when injected into the lateral septum (LS) (Stanley et al., 1988), an area previously linked to several motivational and affective behaviors. The LS has connections to cortical and subcortical regions associated with motivation, and emotion, which makes it a potentially important integrative site for control and modulation of feeding-related behaviors. In this dissertation, I sought to establish receptor specificity, site-specificity and behavioral specificity of opioid-stimulation induced feeding in the LS.I replicated the robust feeding effects found by Stanley et al. (1988) at a lower morphine dose of 5 µg and found that this effect was reliable across days. I found that naloxone (a competitive opioid receptor antagonist) attenuated the feeding effect of morphine without changing baseline food intake, suggesting that the elicited feeding is likely specific to opioid receptors. I found that both the mu specific receptor agonist DAMGO and the GABA agonist muscimol increased feeding behavior when injected into the lateral septum. The effects of morphine were blocked at high doses by the mu specific receptor antagonist CTAP, suggesting that both mu opioid and GABA receptors may play a similar role in the modulation of feeding behaviors by the lateral septum.Although there are many sites in the brain in which stimulation of opioid receptors might stimulate feeding there are differences in feeding response to mu opioid and GABA agonists within the lateral septum. Specifically, muscimol was effective in the ventral and rostral lateral septum, while opioids are more effective in the medial septum, even more than the lateral septum. This interesting finding could reflect interactions of opioid and GABAergic receptors or receptor distribution within the septum. It may mean that the septal control of feeding and motivation involves multiple mechanisms in multiple regions